Liver failure (LF) is a pathological condition characterized by a certain symptom of a violation of the functioning of this organ (hepatitis, hepatomegaly, cholestasis, hyperbilirubinemia, ascites, hypoglycemia, encephalopathy), which occurs as a result of exposure to certain exogenous (toxins, viruses) or endogenous (metabolites, autoimmune factors) factor. In 13-20% of cases, the cause of LF in children is hereditary metabolic disorders, the most common tyrosinemia type I, citrullinemia type I, galactosemia, isolated deficiency of long chain 3-hydroxyacyl CoA dehydrogenase methylmalonic acidemia. Since the liver plays a key role in most metabolic pathways in the human body, the LF of any etiology causes complex changes in the metabolic status of the patient. Such secondary metabolic changes often mimic hereditary metabolic diseases and require a clear differentiation from the primary metabolic signs of hereditary metabolic disorders in order to avoid false-positive or false-negative diagnosis of this pathology. Purpose of the study. Development of criteria for the delimitation of primary and secondary changes of amino acids and acylcarnitines concentration in dry blood spots of children with liver failure. Results and discussion. The results of the study of 480 dry blood spots in patients with clinical and / or functional liver failure and 264 blood spot specimens in the group of referrals have been analyzed. It has been shown that in the 300 patients from the group of patients with LF (62.5%), the level of specific amino acids went beyond the reference values. Of these 300 patients, 25 patients were diagnosed, among them galactosemia in 6 patients, tyrosinemia type I in 5, LCHADD in 9, citrullinemia type I in 1 and MMA in 5. In the other 275 patients the following features of the metabolite profile were revealed: 54 patients had a higher concentration of tyrosine, 41 – methionine, 54 increased levels of acylcarnitine C3, 51 increased C2 levels, and 57 increased C0, at 76 – С14, at 52 – С16: 1, at 63 – С16 and at 39 – С14: 1. Moreover, 236 people were found to increase the level of two or more metabolites. The ROC analysis of the criteria for interpreting the results of tandem mass spectrometry for the diagnosis of tyrosinemia type I has shown that the application of the new reference value of tyrosine concentration (> 312 μmol/l) increases the specificity of the method from 87.1% to 98.3%, since in two patients with galactosemia tyrosine was more than 312 μmol/l. The ROC analysis of the new method for interpreting the results of selective screening of hereditary metabolic diseases, in particular, MMA, showed an increase in the specificity of this method from 90.4% to 94.9%, since two patients with C3 values above 6.43 had a deficiency of vitamin B12, but not methylmalonic acidemia. Also, we proposed the new ratio (C16OH + C18OH + C18: 1OH) / (C0 + C2)> 0.025, which takes into account the C2 index and cuts all false-positive results and increase the specificity of diagnostic method from 78,3 to 100%. All these criteria allow to speed up the time conducting the diagnostic process and setting the final diagnosis. In addition, in patients with liver failure without diagnosis of inherited disorder were detected the following metabolic profiles C2, C18: 2, C18: 1, C16, C0 and C3, as well as C16, C16: 1 and C14. Summary. To optimize the interpretation of the results of selective screening of patients with LF of unclear genesis, it was suggested to use a tyrosine concentration of > 312 μmol/l as the upper limit for the diagnosis of tyrosinemia type I, which increases the specificity of the diagnostic method from 87,1% to 98,3%, C3 concentration > 6,43 μmol/l for the diagnosis of methylmalonic acidemia, which increases the specificity of diagnosis of MMA from 90,4% to 94,9%, as well as the use of the ratio (C16OH + C18OH + C18: 1OH) / (C0 + C2)> 0,025 increases specificity of diagnosis LCHAD deficiency from 78,3 to 100%. Such measures will help speed up the diagnostic process and make a final diagnosis that is especially important for patients with liver failure.
